Lặn nín thở như một phản ứng sinh tồn của não Dịch bởi AI Walter de Gruyter GmbH - - 2013
Željko Dujić, Toni Brešković, Darija Baković
Tóm tắtCác vận động viên lặn nín thở chuyên nghiệp là những vận động viên độc nhất đối mặt với áp lực do sức nước và tình trạng hạ oxy/hypercapnia cực độ trong các lần lặn tối đa. Kỷ lục thế giới hiện tại dành cho nam giới là 214 mét cho độ sâu (Herbert Nitsch, môn lặn nín thở không giới hạn), 11:35 phút cho thời gian (Stephane Mifsud, môn lặn nín thở tĩnh), và 281 mét cho khoảng cách (Goran Čolak, môn lặn nín thở động với vây). Những thích ứng sinh lý chính cho phép các vận động viên lặn nín thở đạt được độ sâu và thời gian như vậy được gọi là phản ứng "lặn" bao gồm co mạch ngoại biên và tăng huyết áp, nhịp tim chậm, giảm lưu lượng tim, tăng lưu lượng máu não và cơ tim, co tỳ, và duy trì cung cấp O2 cho não và tim. Tổ hợp các thích ứng sinh lý này không chỉ riêng có ở con người mà còn tồn tại ở tất cả các loài động vật có vú lặn. Mặc dù có những thích ứng sinh lý sâu sắc này, các vận động viên lặn có thể thường xuyên gặp tình trạng mất ý thức do thiếu oxy. Quá trình lặn nín thở bắt đầu với một giai đoạn dễ chịu trong đó các cơ hô hấp không hoạt động, trong khi trong giai đoạn thứ hai được gọi là "giai đoạn đấu tranh", các chuyển động thở không tự nguyện bắt đầu xảy ra. Những co thắt này làm tăng lưu lượng máu não bằng cách thúc đẩy khối lượng bơm máu của tâm thất trái, lưu lượng tim, và huyết áp động mạch. Phân tích các cơ chế bù trừ tham gia vào các lần lặn nín thở tối đa có thể cải thiện khả năng sống sót của não trong các điều kiện liên quan đến tình trạng thiếu máu não sâu và thiếu oxy.
Region-specific neuron and synapse loss in the hippocampus of APPSL/PS1 knock-in miceWalter de Gruyter GmbH - Tập 4 - Trang 8-19 - 2013
Ivona Brasnjevic, Roy Lardenoije, Christoph Schmitz, Nicolien Van Der Kolk, Dara L. Dickstein, Hisaaki Takahashi, Patrick R. Hof, Harry W. M. Steinbusch, Bart P. F. Rutten
Transgenic mouse models with knock-in (KI) expression of human mutant amyloid precursor protein (APP) and/or human presenilin 1 (PS1) may be helpful to elucidate the cellular consequences of APP and PS1 misprocessing in the aging brain. Age-related alterations in total numbers of neurons and in numbers of synaptophysin-immunoreactive presynaptic boutons (SIPB), as well as the amyloid plaque load were analyzed in the hippocampal dentate gyrus (DG), CA3, and CA1-2 of 2- and 10-month-old APPSL/PS1 homozygous KI, APPSL (expressing human mutant APP751 carrying the Swedish [K670N/M671L] and London [V717I] mutations under Thy-1 promoter), and PS1 homozygous KI mice (expressing human PS1 mutations [M233T and L235P]). APPSL/PS1 homozygous KI mice, but neither APPSL mice nor PS1 homozygous KI mice, showed substantial agerelated loss of neurons (−47.2%) and SIPB (−22.6%), specifically in CA1-2. PS1 homozygous KI mice showed an age-related increase in hippocampal granule cell numbers (+37.9%). Loss of neurons and SIPB greatly exceeded the amount of local extracellular Aβ aggregation and astrocytes, whereas region-specific accumulation of intraneuronal Aβ preceded neuron and synapse loss. An age-related increase in the ratio of SIPB to neuron numbers in CA1-2 of APPSL/PS1 homozygous KI mice was suggestive of compensatory synaptic plasticity. These findings indicate a region-selectivity in intra- and extraneuronal Aβ accumulation in connection with neuron and synapse loss in the hippocampus of APPSL/PS1 homozygous KI mice.
Diffuse disconnectivity in traumatic brain injury: a resting state fMRI and DTI studyWalter de Gruyter GmbH - Tập 3 - Trang 9-14 - 2012
Cheuk Ying Tang, Emily Eaves, Kristen Dams-O’Connor, Lap Ho, Eric Leung, Edmund Wong, David Carpenter, Johnny Ng, Wayne Gordon, Giulio Pasinetti
Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.
F. K. Studnička (1894): Fishes and amphibians also have the cerebral cortexWalter de Gruyter GmbH - Tập 2 - Trang 79-89 - 2011
Miloš Judaš
The aim of this paper is to provide translation of probably the first report (Studnička 1894) demonstrating that the telencephalon of all vertebrate taxa (including fishes and amphibians) is characterized by the presence of the cerebral cortex (pallium). This report was one of those initiating a century-long and still not fully resolved discussion concerning homologies of various pallial subdivisions in different vertebrate taxa and probably the first to draw attention to the importance of careful study of the pallium in representatives of agnathans (Cyclostomes) such as lampreys (Petromyzonts) and hagfishes (Myxinoids). This article also briefly reviews the current status of comparative research on vertebrate telencephalon, and provides historical notes which position Studnička’s report in its historical context.
Stem cell therapy for neurological disordersWalter de Gruyter GmbH - Tập 2 - Trang 319-324 - 2011
Koraljka Bačić Baronica, Latica Friedrich
Stem cells have long been in focus as potential therapy or even cure for a whole myriad of diseases. Many neurodegenerative disorders, both acute and chronic, are characterized by irreversible neuronal damage and loss, and only a few efficient treatment options exist. In contrast to many other tissues, the potential of self-regeneration of the central nervous system is highly limited. There is hope that stem cells could replace the damaged neuronal and glial cells, and provide biological and functional restoration based on their properties of self renewal and the ability to give rise to different cells. In recent years, the promising results of research on animal models has led to the establishment of the first clinical trials; although no clear evidence of therapeutic benefit for any of the conditions have been ascertained. Here we give a review of the current strategies of stem-cell based therapy for some of the more common neurological disorders, discussing the progress and current challenges, and giving an overview of future perspectives.
Deep brain stimulation facilitates memory in a model of Alzheimer’s diseaseWalter de Gruyter GmbH - - 2010
Isabel Arrieta‐Cruz, Constantine Pavlides, Giulio Maria Pasinetti
AbstractBased on evidence suggesting that deep brain stimulation (DBS) may promote certain cognitive processes, we have been interested in developing DBS as a means of mitigating memory and learning impairments in Alzheimer’s disease (AD). In this study we used an animal model of AD (TgCRND8 mice) to determine the effects of high-frequency stimulation (HFS) on non-amyloidogenic α-secretase activity and DBS in short-term memory. We tested our hypothesis using hippocampal slices (in vitro studies) from TgCRND8 mice to evaluate whether HFS increases α-secretase activity (non-amyloidogenic pathway) in the CA1 region. In a second set of experiments, we performed in vivo studies to evaluate whether DBS in midline thalamic region re-establishes hippocampal dependent short-term memory in TgCRND8 mice. The results showed that application of HFS to isolated hippocampal slices significantly increased synaptic plasticity in the CA1 region and promoted a 2-fold increase of non-amyloidogenic α-secretase activity, in comparison to low frequency stimulated controls from TgCRND8 mice. In the in vivo studies, DBS treatment facilitated acquisition memory in TgCRND8 mice, in comparison to their own baseline before treatment. These results provide evidence that DBS could enhance short-term memory in a mouse model of AD by increasing synaptic transmission and α-secretase activity in the CA1 region of hippocampus.
Pentose-phosphate pathway disruption in the pathogenesis of Parkinson’s diseaseWalter de Gruyter GmbH - Tập 5 - Trang 179-184 - 2014
Laura Dunn, Vanessa Fairfield, Shanay Daham, Juan P. Bolaños, Simon J. Heales
Oxidative stress is known to be a key factor in the pathogenesis of Parkinson’s disease (PD). Neuronal redox status is maintained by glucose metabolism via the pentose-phosphate pathway and it is known that disruption of glucose metabolism is damaging to neurons. Accumulating evidence supports the idea that glucose metabolism is altered in PD and dysregulation of the pentose-phosphate pathway in this disease has recently been shown. In this review, we present an overview of the literature regarding neuronal glucose metabolism and PD, and discuss the implications of these findings for PD pathogenesis and possible future therapeutic avenues.
G protein co-signaling and challenges for translational researchWalter de Gruyter GmbH - Tập 4 - Trang 66-73 - 2013
Irene Litosch
The Gq-linked G protein coupled receptors (GPCRs) and their signaling pathways are important clinical targets for the dementia of Alzheimer’s disease and cognitive decline with aging. Gq stimulates phospholipase C-β1 (PLC-β1) activity, increasing levels of inositol-1, 4, 5-trisphosphate (IP3) and diacylglycerol, to initiate mobilization of intracellular Ca2+ and activation of protein kinase C, respectively. While high concentrations of ligand typically evoke large sustained increases in cytosolic Ca2+ levels, it has long been appreciated that the dynamics of the Ca2+ increase are more complex and consistent with multiple levels of regulation. Physiologically relevant concentrations of Gq-ligands evoke rhythmic fluctuations or an oscillation in the level of cytosolic Ca2+. Downstream targets are tuned to respond to the frequency of the Ca2+ oscillations which in turn, reflect the oscillations in IP3 levels. Oscillatory behavior depends on the assembly of self-organizing interactions. The components that contribute to and regulate the Ca2+ oscillator have been unclear, precluding transfer of this fundamental knowledge from bench to bedside. Many GPCRs that signal with Gq also co-signal with G12. G protein co-signaling could therefore regulate the Ca2+ oscillator. This letter explores the potential relationship between Ca2+ oscillations, G protein co-signaling and cellular response in the context of our recent observations. We found that Gq efficacy is synergistic with phosphatidic acid, (PA), a signaling mediator generated downstream of activated G12 and RhoA. Regulation by PA depends on interaction with the unique PLC-β1 PA binding region. G protein co-signaling is therefore a mechanism for GPCRs to collectively assemble self-organizing interactions that regulate the Ca2+ oscillator.
Cingulum bundle white matter in MAG-knockout miceWalter de Gruyter GmbH - Tập 1 - Trang 131-138 - 2010
Devorah Segal, David Carpenter, Malin Höistad, Vahram Haroutunian, Cheuk Y. Tang, Patrick R. Hof
Myelin associated glycoprotein (MAG) is an oligodendrocyte-derived gene whose expression is decreased in schizophrenia. Several measures of white matter integrity appear abnormal in schizophrenia, specifically in the anterior cingulate gyrus. We studied mice lacking MAG as a potential model of dysmyelination. Using the stereological “Space Balls” method, we estimated myelinated fiber length density in the cingulum bundle in adult knockout and control mice. We performed diffusion anisotropy imaging in these animals, measuring fractional anisotropy (FA) in a region of the cingulum bundle. We found no differences in cingulum myelinated fiber length density between the two groups, although we did note an age-related decrease regardless of genotype. No differences were noted in FA either, but an age-related decrease was seen as well. These findings imply that MAG dysfunction alone is not sufficient to cause the white matter alterations seen in schizophrenia.
Models of CNS injury in the nonhuman primate: A new era for treatment strategiesWalter de Gruyter GmbH - Tập 3 - Trang 181-195 - 2012
Leon Teo, Jeffrey V. Rosenfeld, James A. Bourne
Central nervous system (CNS) injuries affect all levels of society indiscriminately, resulting in functional and behavioral deficits with devastating impacts on life expectancies, physical and emotional wellbeing. Considerable literature exists describing the pathophysiology of CNS injuries as well as the cellular and molecular factors that inhibit regrowth and regeneration of damaged connections. Based on these data, numerous therapeutic strategies targeting the various factors of repair inhibition have been proposed and on-going assessment has demonstrated some promising results in the laboratory environ. However, several of these treatment strategies have subsequently been taken into clinical trials but demonstrated little to no improvement in patient outcomes. As a result, options for clinical interventions following CNS injuries remain limited and effective restorative treatment strategies do not as yet exist. This review discusses some of the current animal models, with focus on nonhuman primates, which are currently being modeled in the laboratory for the study of CNS injuries. Last, we review the current understanding of the mechanisms underlying repair/regrowth inhibition and the current trends in experimental treatment strategies that are being assessed for potential translation to clinical applications.
